靶向衰老细胞以减轻心血管疾病进展。

Targeting senescent cells to attenuate cardiovascular disease progression.

机构信息

Center for Molecular and Translational Medicine, Georgia State University, 157 Decatur Street SE, Atlanta, GA, 30303, United States.

Center for Molecular and Translational Medicine, Georgia State University, 157 Decatur Street SE, Atlanta, GA, 30303, United States.

出版信息

Ageing Res Rev. 2020 Jul;60:101072. doi: 10.1016/j.arr.2020.101072. Epub 2020 Apr 13.

Abstract

Cardiovascular disease (CVD) is the most common disease to increase as life expectancy increases. Most high-profile pharmacological treatments for age-related CVD have led to inefficacious results, implying that novel approaches to treating these pathologies are needed. Emerging data have demonstrated that senescent cardiovascular cells, which are characterized by irreversible cell cycle arrest and a distinct senescence-associated secretory phenotype, accumulate in aged or diseased cardiovascular systems, suggesting that they may impair cardiovascular function. This review discusses the evidence implicating senescent cells in cardiovascular ageing, the onset and progression of CVD, and the molecular mechanisms underlying cardiovascular cell senescence. We also review eradication of senescent cardiovascular cells by small-molecule-drug-mediated apoptosis and immune cell-mediated efferocytosis and toxicity as promising and precisely targeted therapeutics for CVD prevention and treatment.

摘要

心血管疾病(CVD)是随着预期寿命延长而最常见的增加的疾病。大多数针对与年龄相关的 CVD 的高知名度的药理学治疗方法都导致了无效的结果,这意味着需要新的方法来治疗这些病变。新出现的数据表明,衰老的心血管细胞在衰老或患病的心血管系统中积累,这些细胞的特征是不可逆的细胞周期停滞和独特的衰老相关分泌表型,这表明它们可能损害心血管功能。本综述讨论了衰老细胞在心血管衰老、CVD 的发生和进展以及心血管细胞衰老的分子机制中的作用。我们还回顾了通过小分子药物介导的细胞凋亡和免疫细胞介导的胞吐作用清除衰老的心血管细胞,作为预防和治疗 CVD 的有前途和精确靶向的治疗方法。

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